Could inhibiting the DPP4 enzyme help treat coronavirus?

Summary: Previous studies of related coronaviruses SARS and MERS found blocking DPP4 activity reduced inflammatory response. Researchers suggest drugs that target DPP4 could help to reduce the overexpression of inflammatory cytokines seen in severe COVID-19.

Source: University of Miami

Researchers and clinicians are scrambling to find ways to combat COVID-19, including new therapeutics and eventually a vaccine. In a commentary published in the journal Diabetes Research and Clinical Practice, Miller School of Medicine professor and endocrinologist Gianluca Iacobellis, M.D., Ph.D., suggests the DPP4 enzyme presents an interesting target for further research, and DPP4 inhibitors could help some COVID-19 patients.

“We potentially have a mechanism for how the virus is getting into the body,” said Dr. Iacobellis. “And we potentially have a way we can partially inhibit that mechanism. We should consider clinical trials for DPP4 for patients who have mild or moderate COVID-19 with type 2 diabetes.”

DPP4 is found throughout the body, but its activity is only partially understood. The enzyme does play significant roles in inflammatory responses and insulin regulation. DPP4 inhibitors increase insulin and GLP-1 secretion and are commonly prescribed for people suffering from type 2 diabetes.

In the current crisis, type 2 diabetes patients are at much higher risk. Data from Wuhan and Italy have shown they have higher mortality and higher ICU admission rates. Building on previous research, conducted on earlier coronaviruses, as well as a recent paper that demonstrates DPP4 interaction with COVID-19, Dr. Iacobellis believes the enzyme may play a significant role in these outcomes by interfering with the immune response.

“The body is overreacting with this inflammatory response to the virus,” said Dr. Iacobellis. “This could be partially mediated by DPP4. The virus binds to the enzyme and the enzymatic activity of DPP4 overexpresses inflammatory cytokines, exaggerating the inflammatory response. Previous studies, of SARS and MERS, showed that, if you blocked DPP4 activity, there was a reduction in the inflammatory response. This could ameliorate the immune response to the virus.”

This shows the interaction between dpp4 and covid19
How the DPP4 enzyme and COVID-19 interact. The image is credited to Vankadari N and Wilce JA, Emerging Microbes and Infections / DOI:10.1080/22221751.2020.1739565.

Dr. Iacobellis notes that clinicians will need more data before embracing DPP4 inhibitors to treat COVID-19 patients. However, he also points out that early evidence has shown these drugs reduce inflammation. He believes the enzyme’s potential role in a COVID-19 therapeutic regimen certainly deserves further study.

“Starting with diabetes patients, we should be conducting randomized studies to test whether treating those with mild or moderate symptoms improves outcomes,” said Dr. Iacobellis. “These drugs are well tolerated and may provide therapeutic benefit.”

About this coronavirus research article

University of Miami
Media Contacts:
Joanna Palmer – University of Miami
Image Source:
The image is credited to Vankadari N and Wilce JA, Emerging Microbes and Infections / DOI:10.1080/22221751.2020.1739565

Original Research: Open access
“COVID-19 and diabetes: Can DPP4 inhibition play a role?”. by Gianluca Iacobellis.
Diabetes Research and Clinical Practice doi:10.1016/j.diabres.2020.108125.


COVID-19 and diabetes: Can DPP4 inhibition play a role?

In general, people with diabetes are at higher risk to develop complications when they are infected with a virus. Type 2 diabetes, the most common type of diabetes, is associated with a low grade chronic inflammation induced by the excessive visceral adipose tissue. This inflammatory status affects the homeostatic glucose regulation and peripheral insulin sensitivity. Chronic hyperglycemia and inflammation can cause an abnormal and ineffective immune response. This complex and multifactorial pathway includes a decreased mobilization of polymorphonuclear leukocytes, chemotaxis, and phagocytic activity, lower secretion of cytokines such as interleukin-1 (IL-1) and IL-6 in response to lipopolysaccharides, inhibition of Tumor Necrosis Alpha (TNFα) activity by T-cells and glycation of immunoglobulin.

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  1. Dear Dr Vandakari,
    hope this finds you well
    I wanted to reach out to you and apologize for the inconvenience.

    In the interview that was published in the University of Miami News I gave full credit to your brilliant discovery.
    There was a link in the interview text clearly linking to your original paper, published in the journal Emerging Microbes and Infections
    It is curious that my commentary on the potential role of DPP4 in COVID-19 published in Diabetes Research and Clinical Practice was accepted before your publication.

    So I wanted to link my intuition with your finding. I agree that the discovery belongs to you and your group, of course.
    I never attributed to myself that. I simply served as “catalytic enzyme” to circulate your discovery and stimulate the research on the possible role of DPP4 inhibition in COVID-19 patient.
    Your discovery is so potentially important that I cited it in another scientific paper that will be published soon in Obesity.
    Unfortunately, the figure, that was added by the author of the interview with the sole intention to illustrate your point and discovery, was not linked to the link to your paper that we had in the interview and that created the misleading information in the news.

    UM news office immediately removed it from the interview.

    I request here that NeuroscienceNews will credit the image to you and your group

    Again I truly apologize for the inconvenience.

    I take this opportunity to congratulate again with you and your team and offer my availability to work together on improving our knowledge on the role of DPP4/CD26 and DPP4 inhibition in COVID-19 patients

    I look forward to hearing from you


    Gianluca Iacobellis MD PhD
    Professor of Medicine
    Director of University of Miami Hospital Diabetes Service
    Division of Endocrinology, Diabetes and Metabolism
    Department of Medicine
    University of Miami, FL

  2. Dear Editor,

    It was unethical to notice that the figure showing “How the DPP4 enzyme and COVID-19 interact. The image is credited to Dr. Gianluca Iacobellis.” doest not belong to Dr. Gianluca Iacobellis. It was my publication and published in the journal Emerging Microbes and Infections (EMI). (DOI:10.1080/22221751.2020.1739565). It is also the sole property of Monash University and the respective journal (EMI and Tayler and Francis) but belong to either Dr. Gianluca Iacobellis or the University of Miami. Our group is the first to publish and tell the possible role of COVID19 spike glycoprotein and CD26 (DPP4). This news article and the published article raised ethical concern and the same has been passed on to the Journal editors, ethics depart of the Miami and Monash University.

    1. Dear Dr. Vankadari,

      Thank you so much for letting us know. We publish based on the information we are provided by various sources, so I deeply apologize for the incorrect credit within this post.

      I am publishing your comment, along with that of Dr. Gianluca in response to your post for clarity. I will also update the figure citing you, Monash and EMI as the sources.

      Please feel free to contact us if you require more information.

      Again, thank you very much for your input and comment. We strive to be as accurate as possible and give credit where it is due.

      1. Dear Admin,
        Thanks for your reply and taking a step forward in correcting.
        It needs to cite the correct way,
        Vankadari N and Wilce JA, Emerging Microbes and Infections / DOI:10.1080/22221751.2020.1739565″ (with the DOI or journal name and must hyperlinked to the original article in EMI)
        I did not see the hyperlink referring to the original article.
        I did not give the figure or data. So it needs to be cited as indicated above.
        Thank you.
        Dr. Naveen Vankadari
        Research Fellow
        Monash University

        1. Dr. Vankadari,

          The update has been made as requested. Please check the image source link at the end of the article and you will see the correct citation with a link to the paper in EMI via the DOI. We can not add the DOI link under the image directly, but the citation is implemented as requested there.

          Thank you again for providing the correct information and for all your hard work.

Comments are closed.